Preliminary study from our laboratory has indicated that some properties of membrane-dependent (Na ion plus K ion)-ATPase in mammalian brain were altered during aging. Since the fatty acyl group composition of neuronal membranes is unique and unsaturated, lipid peroxidation of membranes may cause the observed changes. The proposed study is designed to reevaluate the hypothesis that cellular membranes may provide a site for initiating the aging process. Specifically, we will: 1) study the effect of aging on structure and function of CNS membranes, 2) examine the effect of aging on membrane-dependent active transport processes related to synaptic transmission and 3) evaluate the effect of dietary antioxidants on structure and function of CNS membrane. Correlations involving protective actions of antioxidants on life span, lipofuscin pigment formation and other neurochemic parameters will be delineated. Synaptosomal particles will be isolated from cerebral cortex of rat brain by differential and density gradient centrifugation. Active uptake of putative neurotransmitters (norepinephrine, serotonin, GABA) and active transport of choline by isolated synaptosomal particles will be examined among young, middle-aged and old rats. Possible changes in the structure and function of synaptosomal membrane during aging will be investigated by kinetic studies of membrane-bound (Na ion plus K ion)-ATPase and by examination of membrane composition, such as cholesterol, phospholipid and acyl group content as well as the protein profiles. In addition, the formation of age pigments, life span and membrane-dependent transport activities will be assessed in rats fed antioxidants such as vitamin E, selenium compounds and butylated hydroxytoluene. It is anticipated that the results of this investigation will lead to new insight regarding the cellular basis of aging which may be important in providing possible therapeutic measures for a more healthy and effective life for the aged. BIBLIOGRAPHIC REFERENCES: Samorajski, T., Strong, J. R. and Sun, (1977) Dihydroergotoxin (Hydergine) and alcohol-induced variations in young and old mice. J. Gerontol. 32:145-152. Sun, A. Y. and Seaman, R. N. (1977) The effect of aging on synaptosomal Ca2ion-transport in the brain. Expt'l. Aging Res. in press.